Complexation of C₆₀ Fullerene with Aromatic Drugs

Abstract

The contributions of various physical factors to the energetics of complexation of aromatic drug molecules with C(60) fullerene are investigated in terms of the calculated magnitudes of equilibrium complexation constants and the components of the net Gibbs free energy. Models of complexation are developed taking into account the polydisperse nature of fullerene solutions in terms of the continuous or discrete (fractal) aggregation of C(60) molecules. Analysis of the energetics has shown that stabilization of the ligand-fullerene complexes in aqueous solution is mainly determined by intermolecular van der Waals interactions and, to lesser extent, by hydrophobic interactions. The results provide a physicochemical basis for a potentially new biotechnological application of fullerenes as modulators of biological activity of aromatic drugs.

Interceptor effect of C60 fullerene on the in vitro action of aromatic drug molecules

“…It should be noted that the mechanism of biological action of aromatic BACs, such as DOX, EB and PF, may also be viewed in terms of other processes such as enzyme inhibition, direct membrane action or generation of ROS (for reviews, see Evstigneev 2010;Evstigneev et al 2013). The studied drugs are similar in their ability to intercalate into DNA, but are very different in their ability to generate ROS or bind with enzymes or membranes.…”

“…The Kh value for the EB-C6fl system is absent in the literature; therefore, in the subsequent calcula tions, the intermediate value between DOX-C6fl and PF-C6fl constants was used. The reason for this is a significant role of the amino sugar in the structure of the DOX molecule revealed in Evstigneev et al (2013), which envelopes the surface of C6fl fullerene and enhances Kh because of the favorable hydrophobic and van der Waals interactions. A similar effect can be expected in the EB molecule as well due to the presence of the phenolic ring, although it has smaller dimensions.…”

“…This result creates a scientific basis for the new technology of C6fl fullerene application in anticancer therapy based on simultaneous administration of an anticancer drug and a C6fl fullerene. Taking into account that C6fl fullerene has a saturated 7r-electron system and therefore can form com plexes with aromatic DNA intercalators, including antineo plastic antibiotics and mutagens Evstigneev et al 2013;Mchedlov-Petrossyan et al 2001), it was suggested that a non-covalent complexation in the 'drug-fullerene' system (also referred to as hetero-association) is a key mechanism causing the observed biological synergism . It has been known for quite a long time and so far been observed in proliferat ing cells or bacterial systems [see for review (Evstigneev et al 2008;Evstigneev 2010Evstigneev , 2013] that hetero-association regulates the action of the biologically active compounds during simultaneous administration of combinations of dif ferent aromatic molecules, one of which is the main drug of interest, and the other one is an interceptor molecule.…”

“…These drugs form stable non-cova lent complexes with C6fl fullerene Evstigneev et al 2013) and were previously characterized as the ligands that follow the mechanism of interceptor/ protector action when used in combination with various types of aromatic interceptor molecules (Buchelnikov et al 2012;Evstigneev et al 2006Evstigneev et al , 2008Evstigneev 2010Evstigneev , 2013Larsen et al 1996;Piosik et al 2010;Traganos et al 1991).…”

General statistical-thermodynamical treatment of one-dimensional multicomponent molecular hetero-assembly in solution

“…Non-covalent hetero-assembly of small molecules in solution is currently attracting great attention due to extensive use of this phenomenon in molecular electronics [1][2][3], laser physics [4,5], supramolecular chemistry [2,[6][7][8][9], advanced materials [10][11][12][13], numerous biochemical applications [2,14,15] etc. The key feature of this process is the formation of nanoscale aggregates, which modify the macroscopic physical properties of solute resulting in outcomes of practical importance ranging from discovering of new perspective materials to treatment of human diseases [16].…”